Insights into N6-methyladenosine and programmed cell death in cancer

Abstract

N6-methyladenosine (m6A) methylation, the most common form of internal RNA modification in eukaryotes, has gained increasing attention and become a hot research topic in recent years. M6A plays multifunctional roles in normal and abnormal biological processes, and its role may vary greatly depending on the position of the m6A motif. Programmed cell death (PCD) includes apoptosis, autophagy, pyroptosis, necroptosis and ferroptosis, most of which involve the breakdown of the plasma membrane. Based on the implications of m6A methylation on PCD, the regulators and functional roles of m6A methylation were comprehensively studied and reported. In this review, we focus on the high-complexity links between m6A and different types of PCD pathways, which are then closely associated with the initiation, progression and resistance of cancer. Herein, clarifying the relationship between m6A and PCD is of great significance to provide novel strategies for cancer treatment, and has a great potential prospect of clinical application.

5-Azacytidine Inhibits the Activation of Senescence Program and Promotes Cytotoxic Autophagy during Trdmt1-Mediated Oxidative Stress Response in Insulinoma β-TC-6 Cells

“…Moreover, 5-azaC post-treatment diminished the pools of m 6 A compared to untreated control β-TC-6 cells ( p < 0.001, Figure 6 B). N 6 -methyladenosine, the most abundant modification on mRNAs in eukaryotes, is a methylation event that occurs in the N 6 -position of adenosine that is regulated by m 6 A methyltransferases (writers), m 6 A demethylases (erasers), and binding proteins (readers) [ 45 , 46 , 47 ]. The m 6 A motifs can affect RNA metabolism by the modulation of translation, splicing, export, degradation, and microRNA processing that is implicated in the regulation of physiological functions as well as pathological processes such as cancer [ 45 , 46 , 47 ].…”

“…N 6 -methyladenosine, the most abundant modification on mRNAs in eukaryotes, is a methylation event that occurs in the N 6 -position of adenosine that is regulated by m 6 A methyltransferases (writers), m 6 A demethylases (erasers), and binding proteins (readers) [ 45 , 46 , 47 ]. The m 6 A motifs can affect RNA metabolism by the modulation of translation, splicing, export, degradation, and microRNA processing that is implicated in the regulation of physiological functions as well as pathological processes such as cancer [ 45 , 46 , 47 ]. The role of m 6 A during carcinogenesis is rather complex as both cancer-promoting (induction of oncogene expression and inhibition of tumor suppressor gene expression) and cancer-suppressing (inhibition of oncogene expression and induction of tumor suppressor gene expression) functions of m 6 A were postulated [ 45 , 46 , 47 ].…”

“…The m 6 A motifs can affect RNA metabolism by the modulation of translation, splicing, export, degradation, and microRNA processing that is implicated in the regulation of physiological functions as well as pathological processes such as cancer [ 45 , 46 , 47 ]. The role of m 6 A during carcinogenesis is rather complex as both cancer-promoting (induction of oncogene expression and inhibition of tumor suppressor gene expression) and cancer-suppressing (inhibition of oncogene expression and induction of tumor suppressor gene expression) functions of m 6 A were postulated [ 45 , 46 , 47 ]. M 6 A RNA modification can also control autophagy by targeting selected autophagy-associated genes such as ULK1 , ATG5 , and ATG7 [ 48 , 49 ].…”

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

“…The issue of whether m 6 A methylation exerts anti- or pro-cancer effects remains controversial. The inconsistent results obtained to date may be attributable to distinct characteristics as a result of complex crosstalk of TME and differential regulation of target genes by m 6 A methylation [ 10 ]. However, accumulating evidence suggests that m 6 A methylation promotes the development of multiple diseases, including cancer, under specific circumstances [ 11 – 13 ].…”

Role of N6-Methyladenosine Methylation Regulators in the Drug Therapy of Digestive System Tumours

“…The abnormal levels of m6A modification during the progression of apoptosis, autophagy, ferroptosis, necrosis and pyroptosis have been detected in gastrointestinal tumours ( Zhi et al, 2022 ). Apoptosis, a type of cell death, is closely related to m6A modification ( Zhi et al, 2022 ), wherein it regulates apoptosis by regulating apoptosis-related gene expression, silencing methylation or demethylase genes and reducing YTHDF2-mediated transcripts ( Liu et al, 2022c ). For example, METTL3 inhibits the apoptosis of non-small cell lung cancer (NSCLC) cells by promoting miR-1246 maturation and down-regulating PEG3 expression levels ( Huang et al, 2021 ).…”